Blood sampling for laboratory testing is a major cause of iatrogenic blood loss and anemia in neonatal intensive care unit [NICU] patients. The objective of the study was to assess whether the implementation of a multi-parameter Point of Care Test [POCT] (Roche, Cobas b221) analyzer affected blood loss for central laboratory testing and need for red blood cell transfusion in our NICU. This was a retrospective observational cohort study in a NICU with comparison of two serial cohorts of 2 years each. Implementation of a multi-parameter POCT decreased central laboratory performed testing for bilirubin (−32% per patient) and electrolytes (−36% per patient). On average, the net blood volume taken per admitted patient for electrolyte testing decreased with 23.7% and 22.2% for bilirubin testing in the second cohort. After implementation of POCT, fewer very low birth weight infants [VLBWI] required blood transfusion (38.9% vs. 50%, p < .05) as the number of transfusion/infants decreased by 48% (1.57 vs. 2.53, p < 0.01). The implementation of POCT was cost-efficient for the Belgian national health insurance, cost reduction −8.3% per neonate. We conclude that implementation of a bedside multi-parameter POCT analyzer decreases transfusions among VLBWI by reducing iatrogenic blood loss for central laboratory testing.